Analysis of genetic basis of hereditary unconjugated hyperbilirubinemias and diagnostic criteria

• Project/Area Number: 19591248
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Shiga University of Medical Science
• Principal Investigator: MARUO Yoshihiro Shiga University of Medical Science, 医学部, 講師 (80314160)
• Co-Investigator(Kenkyū-buntansha): SATO Hiroshi 滋賀医科大学, 医学部, 教授 (90090430)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2007: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 小児消化器 / ビリルビンUDP-グルクロン酸転移酵素 / 母乳性黄疸 / Gilbert症候群 / Crigler-Najjar症候群 / UDP-グルクロン酸抱合 / 遺伝薬理学 / 一過性甲状腺機能低下症 / Dual oxidase 2 / 体質性黄疸性 / Crigler-Najjar症候 / 遺伝子解析 / 発現実験

Research Abstract

遺伝性非抱合型高ビリルビン血症(Crigler-Najjar 症候群、Gilbert症候群および母乳性黄疸)100例のビリルビンUDP-グルクロン酸転移酵素遺伝子(UGT1A1)の解析を行なった。遺伝性非抱合型高ビリルビン血症の分子遺伝学的診断基準の作成を提言するのに必要なデータの蓄積ができた。現在、論文を作成し投稿準備中である。

Research Products

• [Journal Article] Hereditary spherocytosis in 3 children coexisting with UDP-glucuronyl transferase 1A1 deficiency (2009)
  • Author(s): Shiota M, Asada J, Nishida H, Kumakura A, Yoshioka T, Hata A, Watanabe K, Maruo Y, et.al.
  • Journal Title: J Pediatr Hematol Oncol. 31 Pages: 121-3
  • Peer Reviewed
• [Journal Article] Hereditary spherocytosis in 3 children coexisting with UDP-glucuronyl transferase 1A1 deficiency. (2009)
  • Author(s): Shiota M, Asada J, Nishida H, Kumakura A, Yoshioka T, Hata A, Watanabe K, Mamo Y, et al.
  • Journal Title: J Pediatr Hematol Oncol 31 Pages: 121-123
  • Peer Reviewed
• [Journal Article] Conformational Change of UGT1A1 by a Novel Missense Mutation (p.L131P) Causing Crigler-Najjar Syndrome Type I (2008)
  • Author(s): Yoshihiro Maruo, Ishwar Chander Verma, Katsuyuki Matsui, et.al.
  • Journal Title: J Pediatr Gastroenterol nutr 46 Pages: 308-311
  • Peer Reviewed
• [Journal Article] Transient congenital hypothyroidism caused by biallelic mutations of the dual oxidase 2(DUOX2)gene in Japanese patients detected by aneonatal screening program (2008)
  • Author(s): Yoshihiro Maruo, Hiroko Takahashi, Ikumi Soeda, et.al.
  • Journal Title: J Clin Endoclinol Metab 93 Pages: 4261-4267
  • Peer Reviewed
• [Journal Article] Effect of D256N and Y483D on propofol glucuronidation by human UDP-glucuronosyltransferase (UGT1A9) (2008)
  • Author(s): Hiroko Takahashi, Yoshihiro Maruo, Asami Mori, et.al.
  • Journal Title: Basic Clin Pharmacol Toxicol 103 Pages: 394-398
  • Peer Reviewed
• [Journal Article] 消化器疾患 体質性黄疸 (2008)
  • Author(s): 丸尾良浩
  • Journal Title: 小児内科 40 Pages: 638-643
• [Journal Article] Conformational change of UGT1A1 by a novel missense mutation (P. L131P) causing Crigler-Najiar syndrome type l (2008)
  • Author(s): Yoshihiro Maruo, Ishwar Chander Verma, Katsuyuki Matsui, et al.
  • Journal Title: J Pediatr Gastroenterol Nutr 46 Pages: 308-311
  • Peer Reviewed
• [Journal Article] Transient congenital hypothyroidism caused by biallelic mutations of the dual oxidase 2 (DUOX2) gene in Japanese patients detected by a neonatal screening program (2008)
  • Author(s): Yoshihiro Maruo, Hiroko Takahashi, lkumi Soeda, et al.
  • Journal Title: J Clin Endoclinol Metab 93 Pages: 4261-4267
  • Peer Reviewed
• [Journal Article] Effect of D256N and Y483D on propofol glucuronidation by human UDP-glucuronosyltransferase (UGT1A9) (2008)
  • Author(s): Hiroko Takahashi, Yoshihiro Maruo, Asami Mori, et al.
  • Journal Title: Basic Clin Pharmacol Toxicol 103 Pages: 394-398
  • Peer Reviewed
• [Journal Article] 体質性黄疸 (2008)
  • Author(s): 丸尾良浩
  • Journal Title: 小児内科 Pages: 40638-40643
• [Journal Article] Conformational Change of UGT1A1 by a Novel Missense Mutation (p.L131P) Ca using Crigler-Najjar Syndrome Type I (2008)
  • Author(s): Maruo Y, et. al.
  • Journal Title: Journal of Pediatric Gastroenterology and Nutrition 46 Pages: 308-311
  • Peer Reviewed
• [Journal Article] Severe hyperbilirubinemia in a 10-year-old girl with a combined disorder of hereditary spherocytosis and Gilbert syndrome (2007)
  • Author(s): Sugita K, Maruo Y, Kurosawa H, Tsuchioka A, Fujiwara T, Mori A, Ideguchi H, eguchi M
  • Journal Title: Pediatr Int 49 Pages: 540-2
  • NAID: 10019815055
  • Peer Reviewed
• [Journal Article] 体質性黄疸の病態と遺伝子異常(特集) (2007)
  • Author(s): 丸尾良浩
  • Journal Title: 小児科診療 70 Pages: 930-935
• [Journal Article] 遺伝性非抱合型高ビリルビン血症(特集) (2007)
  • Author(s): 丸尾良浩
  • Journal Title: 周産期医学 (0386-9881)37巻10 号 Pages: 1323-1327
• [Journal Article] 産科における新生児管理(特集) (2007)
  • Author(s): 柳貴英, 丸尾良浩, 楠田聡
  • Journal Title: 周産期医学 (0386-9881)37巻10号 Pages: 1275-1280
• [Journal Article] Severe hyperbilirubinemia in a 10-year-old girl with a combined disorder of hereditary spherocytosis and Gilbert syndrome (2007)
  • Author(s): Sugita K, Maruo Y, et. al.
  • Journal Title: Pediatric International 49 Pages: 540-542
  • NAID: 10019815055
  • Peer Reviewed
• [Journal Article] 体質性黄疽の病態と遺伝子異常 (2007)
  • Author(s): 丸尾 良浩
  • Journal Title: 小児科診療 70 Pages: 930-935
• [Presentation] UDP-glucuronosyltransferase 1A4 polymorphisms in a Japanese population and kinetics of clozapine glucuronidation (2008)
  • Author(s): Mori A, Maruo Y, Iwai M, et.al.
  • Organizer: The 12^<th> International Glucuronidationand UGT Workshop
  • Place of Presentation: Quebecc City, Canada
  • Year and Date: 2008-07-26
• [Presentation] Combined effect of regulatory polymorphisms of Gilbert syndrome on transcription of UGT1A1 (2008)
  • Author(s): Matsui K, Maruo Y, Sato H, Takeuchi Y
  • Organizer: The 12^<th> International Glucuronidation and UGT Workshop
  • Place of Presentation: Quebec City, Canada
  • Year and Date: 2008-07-26
• [Presentation] Effectof D256N and Y486D on propofol glucuronidation by human UDP-glucuronosyltransf erase (UGT1A9) (2008)
  • Author(s): Ota Y, Takahashi H, Maruo Y, et.al.
  • Organizer: The 12^<th> International Glucuronidation and UGT Workshop
  • Place of Presentation: Quebec City, Canada
  • Year and Date: 2008-07-26
• [Presentation] Differential diagnosis of Gilbert syndrome and Crigler-Najjar syndrome type II based on genotypes ofUGT1A1 (2008)
  • Author(s): Yoshihiro Maruo
  • Organizer: The 12th International Glucuronidation and UGT Workshop
  • Place of Presentation: Quebec City, Canada
  • Year and Date: 2008-07-25
• [Presentation] -過性甲状腺機能低下症家系にみられたDual oxidase 2 (DUOX2)新規変異 (2008)
  • Author(s): 丸尾良浩, 森麻美, 高橋浩子, 等
  • Organizer: 第59回日本小児科学会滋賀地方会
  • Place of Presentation: 大津
  • Year and Date: 2008-05-18
• [Presentation] 母乳性黄疸の遺伝的背景の解明106例の解析 (2008)
  • Author(s): 丸尾良浩, 高橋浩子, 森麻美, 等
  • Organizer: 第111回日本小児科学会学術集会
  • Place of Presentation: 東京
• [Presentation] 発現実験を用いたプレグナンジオールのビリルビUDP-グルクロン酸転移酵素阻害の検討 (2008)
  • Author(s): 丸尾良浩, 三村由卯, 太田依子, 等
  • Organizer: 第111回日本小児科学会学術集会
  • Place of Presentation: 東京
• [Presentation] 寛解導入時の遷延する高ビリルビン血症からGilbert症候群と診断されたALLの1例 (2008)
  • Author(s): 合井久美子, 本名浩子, 廣瀬衣子, 黒田格, 犬飼岳史, 杉田完爾, 高橋和也, 佐藤和正, 丸尾良浩
  • Organizer: 第111回日本小児科学会学術集会
  • Place of Presentation: 東京
• [Presentation] Differential daiagnosis of Gilbert syndrome and Crigler-Najjar syndrome type II based on genotypes of UGT1A1. (2008)
  • Author(s): Maruo Y, Mori A, Takahashi H, et al.
  • Organizer: 11th International Workshop on Glucuronidation
  • Place of Presentation: Quebecc City, Canada
• [Presentation] UDP-glucuronosyltransferase 1A4 polymorphisms in a Japanese population and kinetics of clozapine glucuronidation. (2008)
  • Author(s): Mori A, Maruo Y, Iwai M, et al.
  • Organizer: 11th International Workshop on Glucuronidation
  • Place of Presentation: Quebecc City, Canada
• [Presentation] Combined effect of regulatory polymorphisms of Gilbert syndrome on transcription of UGT1A1. (2008)
  • Author(s): Matsui K, Maruo Y, Sato H, Takeuchi Y.
  • Organizer: 11th International Workshop on Glucuronidation
  • Place of Presentation: Quebecc City, Canada
• [Presentation] Effect of D256N and Y486D on propofol glucuronidation by human UDP-glucuronosyltransferase (UGT1A9) (2008)
  • Author(s): Ota Y, Takahashi H, Maruo Y, et al.
  • Organizer: 11th International Workshop on Glucuronidation
  • Place of Presentation: Quebecc City, Canada
• [Presentation] Dual oxidase 2 (DUOX2)遺伝子のbiallelic mutationによる-過性甲状腺機能低下症の8例と8つの新規変異 (2008)
  • Author(s): 丸尾良浩, 森麻美, 高橋浩子, 松井克之, 三村由卯, 太田依子, 佐藤浩, 竹内義博.
  • Organizer: 第42回日本小児内分泌学会
  • Place of Presentation: 米子
• [Presentation] トルコ人Crigler-Najjar症候群II型にみられたビリルビンUDP-グルクロン酸転移酵素(UGTIAI)遺伝子の新規変異. (2008)
  • Author(s): 丸尾良浩1), Funda Ozgenc2), 三村由卯, 等
  • Organizer: P450&UGT研究会
  • Place of Presentation: 博多
• [Presentation] 遺伝性非抱合型ビリルビン型(Gilbert症候群、Crigler-Najjar症候群)の遺伝子様式は147例の解析より (2007)
  • Author(s): 丸尾 良浩
  • Organizer: 日本小児栄養消化器肝臓学会
  • Place of Presentation: 山形市
  • Year and Date: 2007-11-15